There are several aspects of human brain tumor gene therapy, which are poorly understood in part due to[unreadable] the lack of efficient tools to visualize biological processes in vivo. For example, it is difficult to image immune[unreadable] response during viral oncolysis (Project 1) and to determine the long-term fate of genetically engineered Tcell[unreadable] or progenitor cells (Project 3). The overall goal of this Project is to develop and optimize in vivo imaging[unreadable] techniques that can ultimately be used to objectively monitor vector and cell based glioma therapies. The[unreadable] maging strategies utilized in this Project are based on previously developed agents (e.g. targeted CLIO,[unreadable] activatable NIRF) adapted to high throughput screening for rapid development. In the first aims, we will[unreadable] develop injectable cell-specific imaging agents to image native immune cells (CD4, CDS, NK, macrophages)[unreadable] in their micro-environments using phage and library screens. In parallel we will develop high-efficiency multilabel[unreadable] cell trackers to follow ex vivo labeled cells by different imaging modalities simultaneously. In the second[unreadable] aim we shall develop and validate novel imaging agents that are predictive of the efficacy of oncolytic antiglioma[unreadable] therapies, in particular targets (e.g. aminopeptidase N) that will emerge through rigorous screens.[unreadable] The goal of the third aim is to develop and validate novel constructs to not only follow neural progenitor cells[unreadable] in vivo but image their differentiation into terminal cells as a function of time, delivery routes, and microenvironments.[unreadable] Data from these studies should be highly useful to rapidly evaluate the therapeutic efficacy of[unreadable] cell-based therapies and to develop more efficient approaches. There is a high degree of interaction with[unreadable] other Projects and Cores.